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No Neanderthal-derived Y-chromosomes in modern population

An open access study published in The American Journal of Human Genetics has found no evidence of Neanderthal introgression into modern male Y-chromosome despite it being elsewhere in the modern genome. The study is the first in which a Neanderthal Y-chromosome has been sequenced as all the Neanderthal individuals previously sequenced to 0.1x coverage were women. Women do not have a Y-chromosome, so men inherit their Y-chromosomal DNA exclusively from their fathers. The researchers sequenced the Y-chromosome from a male Neanderthal from the El Sidrón cave site in northern Spain, dating to 49,000 years ago.

The researchers found that the Neanderthal and modern human Y-chromosomes diverged from one another around 588,000 years ago, which is consistent with estimates for when the ancestors of Neanderthals and modern humans diverged from one another. This was not unexpected: the surprise was that no Neanderthal-derived Y-chromosome has ever been observed in a modern male. While this could simply be the result of genetic drift, the researchers found evidence of genetic incompatibility between the Y-chromosomal genes of Neanderthals and modern humans.

They identified protein-coding differences between Neanderthal and modern human Y-chromosomes, including potentially deleterious coding differences in the genes PCDH11Y, TMSB4Y, USP9Y and KDM5D. PCDH11Y and its X-chromosomal counterpart PCDH11X might play a role in brain lateralisation and language development; TMSB4Y might influence sperm production; USP9Y might reduce cell proliferation in malignant tumours; and KDM5D might play a role in suppressing the invasiveness of certain cancers.

Three of these changes are missense mutations, i.e. they alter the amino acid sequence of proteins, which in turn have a biological impact. All three are in genes that produce male-specific minor histocompatibility (H-Y) antigens. Such antigens can trigger an immune response during pregnancy, leading to a miscarriage. These antigens are similar to human leucocyte antigens (HLA) that form part of the body’s immune system, but because the genes are on the Y-chromosome they are specific to men. If only girls were carried to full term, that could explain the absence of any Neanderthal contribution to the present-day Y-chromosome.